We are looking for differences in biochemical traits between strains of rats which have been selected for their susceptibility (S) or resistance (R) to salt-induced hypertension. These biochemical differences can then be analyzed in genetic crosses to determine if the biochemical trait segregates with blood pressure. This will give us information about the genes involved in blood pressure regulation. The R rats accumulate significant amounts of protein (colloid) in Rathke's cleft of their pituitaries. It has been shown that the accumulation of colloid is inversely correlated with blood pressure, indicating that anti-hypertensive factors may be present in colloid. We are now looking for possible components in colloid which may be involved in blood pressure regulation. We are characterizing proteases associated with colloid. The levels of protease activity are significantly higher in R rat pituitaries. We would like to determine whether these proteases are involved in the regulation of peptide hormone processing in the pituitary and ultimately determine their role in blood pressure regulation. We are also examining potential strain differences in mineralocorticoid receptors in S and R rats. This is based upon our finding that the increase in urinary kallikrein activity in response to mineralocorticoids is markedly suppressed in the S rat. We will characterize receptor binding in cytosol and nuclei. We will also compare the proteins induced by mineralocorticoids in S and R renal preparations. Special emphasis will be placed on looking for factors which might block the induction of urinary kallikrein in the S rat.